FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4283777125> ?p ?o ?g. }

• W4283777125 endingPage "S302" @default.
• W4283777125 startingPage "S302" @default.
• W4283777125 abstract "The pancreatic ductal adenocarcinoma (PDAC) has a bad prognosis with delayed diagnosis that significantly impedes the use of therapeutic resection. Similarly, colorectal cancer (CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place in the liver. A main reason for this situation is the already resistant or newly resistant tumors to all conventional current therapies. Here, we report the re-sensitization of PDAC and CRC cells to chemotherapy, radiotherapy and/or immune checkpoint inhibitors by the newly developed inhibitors that target the activity of the proprotein convertases, enzymes involved in the biological activation/maturation of various protein precursors crucial for the malignant phenotype of PDAC and CRC tumors. The in vitro studies include T-cell activation assay performed with plate-bound anti-CD3, qRT-PCR assay and immunocytochemistry for the analysis of the proprotein convertases expression in human cells and tissues. Flow cytometry analysis was performed on single cell suspension of hPBMCs and T cells to analyze PD-1 expression. The activity of the proprotein convertase was assessed by the evaluation of the enzymes' ability to digest the universal PC substrate, the fluorogenic peptide pERTKR-MCA. The analysis of the seven known PC family members, namely, Furin, PC1, PC2, PC4, PACE4, PC5 and PC7, revealed their presence with predominant expression of Furin in PDAC and CRC tissues while compared to non-cancerous tissues from the same patients that associated alteration of the epithelial structure with highly spread expression of Furin all over the tumors. Using computer-aided virtual screening and repurposing approved drug strategies we identify small molecules and repurpose approved drugs against Furin, the only convertase with published crystallographic structure. We generated a collection of 2082 small molecules with 15 molecules identified having an inhibitory Furin activity. Using human cancer organoids in the presence of some of these molecules, the latter were more sensitive to radiotherapy, Gemcitabine and/or 5-fluorouracil. Treatment of activated T cells or PBMCs with these inhibitors repressed significantly PD-1 expression. In preclinical studies using syngeneic mice, 5 molecules were found to significantly reduce tumor progression that associated enhanced survival and sensitivity to radiotherapy of the tumor cells-inoculated mice. The tumor regression was associated with enhanced T cells infiltration in the developed tumors. These findings suggest the potential efficacy of Furin inhibitors in the sensitization of pancreatic and metastatic colon tumors to drug resistance that may contribute to the development of efficient therapeutic strategies and to improve the prognosis of patients with these cancers." @default.
• W4283777125 created "2022-07-03" @default.
• W4283777125 creator A5004469840 @default.
• W4283777125 creator A5036792650 @default.
• W4283777125 creator A5045915307 @default.
• W4283777125 creator A5056746631 @default.
• W4283777125 creator A5069618737 @default.
• W4283777125 creator A5070237613 @default.
• W4283777125 creator A5082524915 @default.
• W4283777125 creator A5084125093 @default.
• W4283777125 creator A5085068319 @default.
• W4283777125 date "2022-06-01" @default.
• W4283777125 modified "2023-09-29" @default.
• W4283777125 title "P-147 Sensitization of pancreatic and colorectal cancer to radiotherapy, chemotherapy, and immune checkpoint inhibitors by newly developed proprotein convertase inhibitors" @default.
• W4283777125 doi "https://doi.org/10.1016/j.annonc.2022.04.237" @default.
• W4283777125 hasPublicationYear "2022" @default.
• W4283777125 type Work @default.
• W4283777125 citedByCount "0" @default.
• W4283777125 crossrefType "journal-article" @default.
• W4283777125 hasAuthorship W4283777125A5004469840 @default.
• W4283777125 hasAuthorship W4283777125A5036792650 @default.
• W4283777125 hasAuthorship W4283777125A5045915307 @default.
• W4283777125 hasAuthorship W4283777125A5056746631 @default.
• W4283777125 hasAuthorship W4283777125A5069618737 @default.
• W4283777125 hasAuthorship W4283777125A5070237613 @default.
• W4283777125 hasAuthorship W4283777125A5082524915 @default.
• W4283777125 hasAuthorship W4283777125A5084125093 @default.
• W4283777125 hasAuthorship W4283777125A5085068319 @default.
• W4283777125 hasBestOaLocation W42837771251 @default.
• W4283777125 hasConcept C121608353 @default.
• W4283777125 hasConcept C126322002 @default.
• W4283777125 hasConcept C181199279 @default.
• W4283777125 hasConcept C2777265534 @default.
• W4283777125 hasConcept C2777701055 @default.
• W4283777125 hasConcept C2778163477 @default.
• W4283777125 hasConcept C2778824825 @default.
• W4283777125 hasConcept C2780072125 @default.
• W4283777125 hasConcept C2780210213 @default.
• W4283777125 hasConcept C2780851360 @default.
• W4283777125 hasConcept C2908627167 @default.
• W4283777125 hasConcept C43554185 @default.
• W4283777125 hasConcept C502942594 @default.
• W4283777125 hasConcept C526805850 @default.
• W4283777125 hasConcept C55493867 @default.
• W4283777125 hasConcept C71924100 @default.
• W4283777125 hasConcept C86803240 @default.
• W4283777125 hasConceptScore W4283777125C121608353 @default.
• W4283777125 hasConceptScore W4283777125C126322002 @default.
• W4283777125 hasConceptScore W4283777125C181199279 @default.
• W4283777125 hasConceptScore W4283777125C2777265534 @default.
• W4283777125 hasConceptScore W4283777125C2777701055 @default.
• W4283777125 hasConceptScore W4283777125C2778163477 @default.
• W4283777125 hasConceptScore W4283777125C2778824825 @default.
• W4283777125 hasConceptScore W4283777125C2780072125 @default.
• W4283777125 hasConceptScore W4283777125C2780210213 @default.
• W4283777125 hasConceptScore W4283777125C2780851360 @default.
• W4283777125 hasConceptScore W4283777125C2908627167 @default.
• W4283777125 hasConceptScore W4283777125C43554185 @default.
• W4283777125 hasConceptScore W4283777125C502942594 @default.
• W4283777125 hasConceptScore W4283777125C526805850 @default.
• W4283777125 hasConceptScore W4283777125C55493867 @default.
• W4283777125 hasConceptScore W4283777125C71924100 @default.
• W4283777125 hasConceptScore W4283777125C86803240 @default.
• W4283777125 hasLocation W42837771251 @default.
• W4283777125 hasOpenAccess W4283777125 @default.
• W4283777125 hasPrimaryLocation W42837771251 @default.
• W4283777125 hasRelatedWork W1568178986 @default.
• W4283777125 hasRelatedWork W1971603734 @default.
• W4283777125 hasRelatedWork W1993619070 @default.
• W4283777125 hasRelatedWork W2023374250 @default.
• W4283777125 hasRelatedWork W2078256947 @default.
• W4283777125 hasRelatedWork W2108397825 @default.
• W4283777125 hasRelatedWork W2133014094 @default.
• W4283777125 hasRelatedWork W2153103577 @default.
• W4283777125 hasRelatedWork W2504209761 @default.
• W4283777125 hasRelatedWork W4232292935 @default.
• W4283777125 hasVolume "33" @default.
• W4283777125 isParatext "false" @default.
• W4283777125 isRetracted "false" @default.
• W4283777125 workType "article" @default.